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PDBsum entry 5zkp
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Signaling protein
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PDB id
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5zkp
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References listed in PDB file
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Key reference
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Title
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Structural basis for signal recognition and transduction by platelet-Activating-Factor receptor.
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Authors
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C.Cao,
Q.Tan,
C.Xu,
L.He,
L.Yang,
Y.Zhou,
Y.Zhou,
A.Qiao,
M.Lu,
C.Yi,
G.W.Han,
X.Wang,
X.Li,
H.Yang,
Z.Rao,
H.Jiang,
Y.Zhao,
J.Liu,
R.C.Stevens,
Q.Zhao,
X.C.Zhang,
B.Wu.
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Ref.
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Nat Struct Mol Biol, 2018,
25,
488-495.
[DOI no: ]
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PubMed id
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Abstract
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Platelet-activating-factor receptor (PAFR) responds to platelet-activating
factor (PAF), a phospholipid mediator of cell-to-cell communication that
exhibits diverse physiological effects. PAFR is considered an important drug
target for treating asthma, inflammation and cardiovascular diseases. Here we
report crystal structures of human PAFR in complex with the antagonist SR 27417
and the inverse agonist ABT-491 at 2.8-Å and 2.9-Å resolution, respectively.
The structures, supported by molecular docking of PAF, provide insights into the
signal-recognition mechanisms of PAFR. The PAFR-SR 27417 structure reveals an
unusual conformation showing that the intracellular tips of helices II and IV
shift outward by 13 Å and 4 Å, respectively, and helix VIII adopts an
inward conformation. The PAFR structures, combined with single-molecule FRET and
cell-based functional assays, suggest that the conformational change in the
helical bundle is ligand dependent and plays a critical role in PAFR activation,
thus greatly extending knowledge about signaling by G-protein-coupled receptors.
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